Zika in Pregnant Women: Researchers Determine Susceptibility, Possible Infection Mechanisms

Mizzou investigators find that African strain of Zika is more deadly than the common Asian strain found in the U.S.

March 9th, 2017

COLUMBIA, Mo. – Infection of pregnant women by the Asian strain of Zika virus has been linked to brain abnormalities such as microcephaly in their infants; however, it is not known at what stage of pregnancy the human fetus is most susceptible to the disease. Now, researchers at the University of Missouri have found that the human fetus may be most vulnerable to Zika infection very early in pregnancy and that the lesser-known African strain of Zika might possibly cause nearly immediate death of the placenta. Clues unlocked in this research could lead to the development of stronger defenses in the global fight against Zika.

“Although the placenta is an effective barrier to the transmission of certain diseases and pathogens, the Asian strain, which has been linked to microcephaly in humans, is generally thought to cross through the placenta,” said R. Michael Roberts, an MU Curators Professor of Animal Science, a professor of biochemistry and an investigator in the Bond Life Sciences Center. “Spread mostly by infected mosquitos, incidences of the virus can be found throughout U.S. states and territories where more than 3,100 cases in pregnant women, mainly travelers from countries where the disease is widespread, have been reported to the Centers for Disease Control and Prevention.”

Roberts and his team, including Megan A. Sheridan, a graduate student in Roberts’ lab, created placental cells from an approved line of pluripotent stem cells that were similar to early stage placentas. These placental cells were then infected with an Asian and African strain of Zika virus to determine how the placental cells were affected by the viruses.

“Zika enters its target cells in a complex, multistep process,” Sheridan said. “We found that the Asian strain of the virus infected and replicated in the cells; however, it didn’t kill the cells as readily. Our research suggests that the Asian strain infects the placenta in the early stages of pregnancy and essentially ‘lies in wait’ where it is then transmitted to the fetus causing neurological disorders in infants such as microcephaly.”

However, the team noticed substantially different results when placental cells were introduced to the African strain of the Zika virus. When exposed, placental cells were killed within days, indicating that African strain of Zika could possibly cause abortions in infected mothers.

“The results from our testing of the African strain were unexpected,” Roberts said. “The cells were killed within 40-48 hours meaning that African Zika, while less prevalent, could be much more deadly during early pregnancy. The findings suggest that the developing fetus could be most vulnerable to infection by Zika virus and other pathogens during a relatively narrow window within the first trimester of pregnancy.”

The Asian strain of Zika virus, which is most prevalent in the Americas and U.S. territories, is more closely linked to microcephaly and other neurological disorders in infants. Knowledge gained through these studies will be helpful in developing strategies and possible vaccines to combat the virus, Sheridan says.

The study, “Vulnerability of primitive human placental trophoblast to Zika virus,” recently was published in the Proceedings of the National Academy of Sciences (PNAS) and was funded in part by the National Institutes of Health (Grants R01HD077108; R01HD067759) and Fundação de Amparo a Pesquisa do Estado de São Paulo (Grant 2014/03620-2). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.